检验医学 ›› 2025, Vol. 40 ›› Issue (6): 615-620.DOI: 10.3969/j.issn.1673-8640.2025.06.017
收稿日期:
2024-02-18
修回日期:
2024-12-04
出版日期:
2025-06-30
发布日期:
2025-07-01
通讯作者:
逯素梅
作者简介:
逯素梅,E-mail:lsmqianyi@126.com。基金资助:
CAO Shuxian, GAO Yinan, SONG Yufan, LU Sumei()
Received:
2024-02-18
Revised:
2024-12-04
Online:
2025-06-30
Published:
2025-07-01
Contact:
LU Sumei
摘要:
脂质过氧化是指细胞中的多不饱和脂肪酸(PUFA)在酶促或者非酶促的作用下产生一系列过氧化产物的过程。脂质过氧化会导致生物膜结构紊乱和功能损伤,进而引起多种疾病,尤其是糖脂代谢紊乱相关疾病,如2型糖尿病、非酒精性脂肪性肝病和心血管疾病。文章总结了脂质过氧化的3种途径,介绍每种途径中发生的主要反应,提炼主要的氧化代谢产物。同时,阐述了3种脂质过氧化途径与疾病发生的关系,重点阐述多种氧化代谢产物对疾病发生、发展的影响。文章旨在对未来脂代谢紊乱相关疾病的治疗,以及新型生物标志物研究提供理论指导。
中图分类号:
曹姝贤, 高毅男, 宋御繁, 逯素梅. 脂质过氧化在糖脂代谢紊乱中的作用研究进展[J]. 检验医学, 2025, 40(6): 615-620.
CAO Shuxian, GAO Yinan, SONG Yufan, LU Sumei. Research progress of lipid peroxidation in dysregulation of glucose and lipid metabolism[J]. Laboratory Medicine, 2025, 40(6): 615-620.
同工酶 | 氧化代谢产物 | 酶的分布 | 功能 |
---|---|---|---|
COX | PGG2、PGH2、PGX2、TXA2 | 全身各处 | 血小板活化,抑癌或促癌,抑炎,水盐平衡或激素分泌 |
LOX | HPETE①、HETE、EET、LX、LT | 表皮、白细胞、肥大细胞、树突状细胞、淋巴细胞等 | 参与哮喘的形成,参与动脉粥样硬化的发生,促炎,抑炎,参与鱼鳞病的发生 |
CYP450 | EET、HETE | 全身各处 | 抑炎或促炎,参与高血压、糖尿病、肿瘤的发展 |
表1 PUFA 3种代谢途径同工酶及其功能
同工酶 | 氧化代谢产物 | 酶的分布 | 功能 |
---|---|---|---|
COX | PGG2、PGH2、PGX2、TXA2 | 全身各处 | 血小板活化,抑癌或促癌,抑炎,水盐平衡或激素分泌 |
LOX | HPETE①、HETE、EET、LX、LT | 表皮、白细胞、肥大细胞、树突状细胞、淋巴细胞等 | 参与哮喘的形成,参与动脉粥样硬化的发生,促炎,抑炎,参与鱼鳞病的发生 |
CYP450 | EET、HETE | 全身各处 | 抑炎或促炎,参与高血压、糖尿病、肿瘤的发展 |
代谢产物 | 功能 | 参考文献 |
---|---|---|
PGI2 | 促炎,促进脂肪细胞分化 | [ |
PGE2 | 抑制前脂肪细胞分化,促进结肠癌发生、发展,抑制癌细胞凋亡,促进癌细胞增殖、侵袭和转移 | [ |
PGD2 | 参与哮喘形成,促炎 | [ |
PGF2α | 使血管收缩、血压升高,参与抑制脂肪生成 | [ |
TX | 诱导血小板活性、诱导血管生成 | [ |
表2 COX途径代谢产物及其功能
代谢产物 | 功能 | 参考文献 |
---|---|---|
PGI2 | 促炎,促进脂肪细胞分化 | [ |
PGE2 | 抑制前脂肪细胞分化,促进结肠癌发生、发展,抑制癌细胞凋亡,促进癌细胞增殖、侵袭和转移 | [ |
PGD2 | 参与哮喘形成,促炎 | [ |
PGF2α | 使血管收缩、血压升高,参与抑制脂肪生成 | [ |
TX | 诱导血小板活性、诱导血管生成 | [ |
代谢产物 | 功能 | 参考文献 |
---|---|---|
HETE | 刺激平滑肌细胞收缩、迁移和增殖,激活内皮细胞功能障碍,促炎 | [ |
TX | 抑炎,抗纤维化 | [ |
表3 LOX途径代谢产物及其功能
代谢产物 | 功能 | 参考文献 |
---|---|---|
HETE | 刺激平滑肌细胞收缩、迁移和增殖,激活内皮细胞功能障碍,促炎 | [ |
TX | 抑炎,抗纤维化 | [ |
代谢产物 | 功能 | 参考文献 |
---|---|---|
DHET | 调节炎症,参与动脉粥样硬化发展 | [ |
HETE | 调节血压平衡和水平衡,维持平滑肌细胞收缩 | [ |
EET | 调节肿瘤发生、发展,调节细胞增殖,参与血管生成、促血管舒张和抗炎作用 | [ |
表4 CYP450途径代谢产物及其功能
代谢产物 | 功能 | 参考文献 |
---|---|---|
DHET | 调节炎症,参与动脉粥样硬化发展 | [ |
HETE | 调节血压平衡和水平衡,维持平滑肌细胞收缩 | [ |
EET | 调节肿瘤发生、发展,调节细胞增殖,参与血管生成、促血管舒张和抗炎作用 | [ |
[1] |
JEON S, CARR R. Alcohol effects on hepatic lipid metabolism[J]. J Lipid Res, 2020, 61(4):470-479.
DOI PMID |
[2] |
PENG Y, LI Z, ZHANG Z, et al. Bromocriptine protects perilesional spinal cord neurons from lipotoxicity after spinal cord injury[J]. Neural Regen Res, 2024, 19(5):1142-1149.
DOI PMID |
[3] | BADMUS O O, HILLHOUSE S A, ANDERSON C D, et al. Molecular mechanisms of metabolic associated fatty liver disease(MAFLD):functional analysis of lipid metabolism pathways[J]. Clin Sci(Lond), 2022, 136(18):1347-1366. |
[4] | VIGOR C, BERTRAND-MICHEL J, PINOT E, et al. Non-enzymatic lipid oxidation products in biological systems:assessment of the metabolites from polyunsaturated fatty acids[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2014, 964:65-78. |
[5] | MORITA M, NAITO Y, YOSHIKAWA T, et al. Plasma lipid oxidation induced by peroxynitrite,hypochlorite,lipoxygenase and peroxyl radicals and its inhibition by antioxidants as assessed by diphenyL-1-pyrenylphosphine[J]. Redox Biol, 2016, 8:127-135. |
[6] | ALVAREZ M L, LORENZETTI F. Role of eicosanoids in liver repair,regeneration and cancer[J]. Biochem Pharmacol, 2021, 192:114732. |
[7] | MITCHELL J A, KIRKBY N S. Eicosanoids, prostacyclin and cyclooxygenase in the cardiovascular system[J]. Br J Pharmacol, 2019, 176(8):1038-1050. |
[8] | FREJBORG E, SALO T, SALEM A. Role of cyclooxygenase-2 in head and neck tumorigenesis[J]. Int J Mol Sci, 2020, 21(23):9246. |
[9] | HAJEYAH A A, GRIFFITHS W J, WANG Y, et al. The biosynthesis of enzymatically oxidized lipids[J]. Front Endocrinol(Lausanne), 2020, 11:591819. |
[10] |
FEUSSNER I, WASTERNACK C. The lipoxygenase pathway[J]. Annu Rev Plant Biol, 2002, 53:275-297.
PMID |
[11] | JANSEN C, HOFHEINZ K, VOGEL R, et al. Stereocontrol of arachidonic acid oxygenation by vertebrate lipoxygenases:newly cloned zebrafish lipoxygenase 1 does not follow the Ala-versus-Gly concept[J]. J Biol Chem, 2011, 286(43):37804-37812. |
[12] | PANG Y, LIU X, ZHAO C, et al. LC-MS/MS-based arachidonic acid metabolomics in acute spinal cord injury reveals the upregulation of 5-LOX and COX-2 products[J]. Free Radic Biol Med, 2022, 193(Pt 1):363-372. |
[13] | BALDWIN W S. Phase 0 of the xenobiotic response:nuclear receptors and other transcription factors as a first step in protection from xenobiotics[J]. Nucl Receptor Res, 2019, 6:101447. |
[14] | ZHOU M, LI J, XU J, et al. Exploring human CYP4 enzymes:physiological roles,function in diseases and focus on inhibitors[J]. Drug Discov Today, 2023, 28(5):103560. |
[15] |
BERGMANN C B, HAMMOCK B D, WAN D, et al. TPPU treatment of burned mice dampens inflammation and generation of bioactive DHET which impairs neutrophil function[J]. Sci Rep, 2021, 11(1):16555.
DOI PMID |
[16] | KELLY K A, HAVRILLA C M, BRADY T C, et al. Oxidative stress in toxicology:established mammalian and emerging piscine model systems[J]. Environ Health Perspect, 1998, 106(7):375-384. |
[17] | NONO NANKAM P A, NGUELEFACK T B, GOEDECKE J H, et al. Contribution of adipose tissue oxidative stress to obesity-associated diabetes risk and ethnic differences:focus on women of African ancestry[J]. Antioxidants(Basel), 2021, 10(4):622. |
[18] | PAN Y, CAO S, TANG J, et al. Cyclooxygenase-2 in adipose tissue macrophages limits adipose tissue dysfunction in obese mice[J]. J Clin Invest, 2022, 132(9):e152391. |
[19] | KARPISHEH V, NIKKHOO A, HOJJAT-FARSANGI M, et al. Prostaglandin E2 as a potent therapeutic target for treatment of colon cancer[J]. Prostaglandins Other Lipid Mediat, 2019, 144:106338. |
[20] | ZHU R, WANG X H, WANG B W, et al. Prostaglandin F2α regulates adipogenesis by modulating extracellular signal-regulated kinase signaling in Graves' ophthalmopathy[J]. Int J Mol Sci, 2023, 24(8):7012. |
[21] | RICHELSEN B. Prostaglandin E2 action and binding in human adipocytes:effects of sex,age,and obesity[J]. Metabolism, 1988, 37(3):268-275. |
[22] | RAHMAN M S. Prostacyclin:a major prostaglandin in the regulation of adipose tissue development[J]. J Cell Physiol, 2019, 234(4):3254-3262. |
[23] | DOMINGO C, PALOMARES O, SANDHAM D A, et al. The prostaglandin D2 receptor 2 pathway in asthma:a key player in airway inflammation[J]. Respir Res, 2018, 19(1):189. |
[24] |
SAMUCHIWAL S K, BOYCE J A. Role of lipid mediators and control of lymphocyte responses in type 2 immunopathology[J]. J Allergy Clin Immunol, 2018, 141(4):1182-1190.
DOI PMID |
[25] | NAJAR M, OUHADDI Y, PARÉ F, et al. Role of lipocalin-type prostaglandin D synthase in experimental osteoarthritis[J]. Arthritis Rheumatol, 2020, 72(9):1524-1533. |
[26] | YAMANE S, AMANO H, ITO Y, et al. The role of thromboxane prostanoid receptor signaling in gastric ulcer healing[J]. Int J Exp Pathol, 2022, 103(1):4-12. |
[27] | ZHANG Y, LIU Y, SUN J, et al. Arachidonic acid metabolism in health and disease[J]. MedComm(2020), 2023, 4(5):e363. |
[28] | SINGH N K, RAO G N. Emerging role of 12/15-lipoxygenase(ALOX15)in human pathologies[J]. Prog Lipid Res, 2019, 73:28-45. |
[29] | 任咪咪, 孙宏志, 马莉, 等. 12/15-脂氧合酶在糖尿病肾脏疾病中的研究进展[J]. 中华肾脏病杂志, 2022, 38(8):754-759. |
[30] | DOBRIAN A D, LIEB D C, MA Q, et al. Differential expression and localization of 12/15 lipoxygenases in adipose tissue in human obese subjects[J]. Biochem Biophys Res Commun, 2010, 403(3):485-490. |
[31] | WANG B, WU L, CHEN J, et al. Metabolism pathways of arachidonic acids:mechanisms and potential therapeutic targets[J]. Signal Transduct Target Ther, 2021, 6(1):94. |
[32] |
HAEGGSTRÖM J Z. Leukotriene biosynthetic enzymes as therapeutic targets[J]. J Clin Invest, 2018, 128(7):2680-2690.
DOI PMID |
[33] | 刘充, 刘迎迎, 郭兆安. 特异性促炎消退介质在糖尿病肾脏疾病中的研究进展[J]. 基础医学与临床, 2023, 43(7):1152-1156. |
[34] | DAS U N. Beneficial role of bioactive lipids in the pathobiology,prevention,and management of HBV,HCV and alcoholic hepatitis,NAFLD,and liver cirrhosis:a review[J]. J Adv Res, 2018, 17:17-29. |
[35] | SOTÁK M, RAJAN M R, CLARK M, et al. Lipoxins reduce obesity-induced adipose tissue inflammation in 3D-cultured human adipocytes and explant cultures[J]. iScience, 2022, 25(7):104602. |
[36] |
ZHA W, EDIN M L, VENDROV K C, et al. Functional characterization of cytochrome P450-derived epoxyeicosatrienoic acids in adipogenesis and obesity[J]. J Lipid Res, 2014, 55(10):2124-2136.
DOI PMID |
[37] |
KROGSTAD V, PERIC A, ROBERTSEN I, et al. A comparative analysis of cytochrome P450 activities in paired liver and small intestinal samples from patients with obesity[J]. Drug Metab Dispos, 2020, 48(1):8-17.
DOI PMID |
[38] | ROCIC P, SCHWARTZMAN M L. 20-HETE in the regulation of vascular and cardiac function[J]. Pharmacol Ther, 2018, 192:74-87. |
[39] | YEN H C, WEI H J, LIN C L. Unresolved issues in the analysis of F2-isoprostanes,F4-neuroprostanes,isofurans,neurofurans,and F2-dihomo-isoprostanes in body fluids and tissue using gas chromatography/negative-ion chemical-ionization mass spectrometry[J]. Free Radic Res, 2015, 49(7):861-880. |
[40] | DALLE-DONNE I, ROSSI R, COLOMBO R, et al. Biomarkers of oxidative damage in human disease[J]. Clin Chem, 2006, 52(4):601-623. |
[41] | ITO F, SONO Y, ITO T. Measurement and clinical significance of lipid peroxidation as a biomarker of oxidative stress:oxidative stress in diabetes,atherosclerosis,and chronic inflammation[J]. Antioxidants(Basel), 2019, 8(3):72. |
[42] | ZHONG S, LI L, SHEN X, et al. An update on lipid oxidation and inflammation in cardiovascular diseases[J]. Free Radic Biol Med, 2019, 144:266-278. |
[43] | SETHIYA N K, GHILORIA N, SRIVASTAV A, et al. Therapeutic potential of myricetin in the treatment of neurological,neuropsychiatric,and neurodegenerative disorders[J]. CNS Neurol Disord Drug Targets, 2024, 23(7):865-882. |
[44] | REDDY P H, OLIVER D M. Amyloid beta and phosphorylated tau-induced defective autophagy and mitophagy in Alzheimer's disease[J]. Cells, 2019, 8(5):488. |
[45] | BREITZIG M, BHIMINENI C, LOCKEY R, et al. 4-Hydroxy-2-nonenal:a critical target in oxidative stress?[J] Am J Physiol Cell Physiol, 2016, 311(4):C537-C543. |
[46] | 麻京豫, 魏经汉, 赵洛沙. 急性冠状动脉综合征8-异前列腺素F2α与血脂、体重指数及腰臀比的相关性研究[J]. 中国综合临床, 2005, 21(9):781-783. |
[47] | DHAM D, ROY B, GOWDA A, et al. 4-Hydroxy-2-nonenal,a lipid peroxidation product,as a biomarker in diabetes and its complications:challenges and opportunities[J]. Free Radic Res, 2021, 55(5):547-561. |
[1] | 赵倩, 曾利敏, 周丽平, 齐林. CYP2C19基因多态性、miR-374b-5p与ACI患者神经功能缺损和近期预后的关系[J]. 检验医学, 2024, 39(6): 536-541. |
[2] | 慎津进, 薛寒, 李进福, 高利飞, 郑业焕. CYP2D6基因分型影响因素研究进展[J]. 检验医学, 2024, 39(3): 291-297. |
[3] | 陈丹, 徐婷, 张洁心, 赵鸿, 戎国栋, 潘世扬, 王芳, 黄珮珺. 实时荧光PCR用于CYP2C19基因多态性检测的性能验证[J]. 检验医学, 2017, 32(9): 801-805. |
[4] | 王文惠, 杨卫华, 堵一乔, 梁发东, 杨振华. ALOX5AP基因单核苷酸多态性与缺血性脑卒中患者颈动脉斑块的相关性分析[J]. 检验医学, 2017, 32(6): 474-480. |
[5] | 鲍芸, 肖艳群, 蒋玲丽, 王雪亮, 杨依绡, 王华梁. 上海地区氯吡格雷药物代谢基因检测室间质量评价[J]. 检验医学, 2017, 32(3): 229-233. |
[6] | 周逸雯, 周琰, 吴炯, 鞠颖慧, 郭玮. CYP3A4、CYP3A5 和CYP2D6 基因单核苷酸多态性对肾移植术后稳定期患者他克莫司代谢的影响[J]. 检验医学, 2015, 30(11): 1091-1095. |
[7] | 牛国平,魏园园. CYP2C9和VKORC1基因多态性与华法林剂量关系的研究[J]. 检验医学, 2014, 29(6): 635-639. |
[8] | 唐玲丽;唐爱国;周后德. shRNA沉默IRS-1基因对鼠前脂肪细胞分化和PPARγ表达的影响[J]. 检验医学, 2010, 25(08): 596-600. |
[9] | 王晓春;张阳德;王铁兵;陈海霞. CYP2E1和GSTM1多态性与再生障碍性贫血遗传易感性研究[J]. 检验医学, 2007, 22(03): 287-290. |
[10] | 陈卫群;王晓春;刘惠宁;胡元佳. 胎儿生长受限孕妇血及脐血内脂过氧化物和一氧化氮水平[J]. 检验医学, 2006, 21(01): 45-47. |
[11] | 李杰萍;梁统;周克元. 5-脂氧合酶在体外培养的大鼠腹腔巨噬细胞中的表达[J]. 检验医学, 2004, 19(03): 250-253. |
[12] | 黄泽红; 肖洪广; 李珉珉; 陈柏铭. 糖尿病患者血清中ox-LDL的检测和临床意义[J]. 检验医学, 1998, 13(1): 16-16. |
[13] | 曹维娟; 赵德育. 婴幼儿毛细支气管炎SOD、MDA、GSH-PX的检测[J]. 检验医学, 1996, 11(1): 6-6. |
[14] | 杨晓群; 姚和祥. 门静脉和周围血铜、锌超氧化物歧化酶含量测定在胆石症患者中的价值[J]. 检验医学, 1994, 9(3): 169-170. |
[15] | 闻平. 用Trinder反应测定血清脂质过氧化氢[J]. 检验医学, 1993, 8(4): 254-254. |
阅读次数 | ||||||
全文 |
|
|||||
摘要 |
|
|||||